{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T13:58:13Z","timestamp":1764251893813,"version":"3.41.2"},"reference-count":24,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T00:00:00Z","timestamp":1721606400000},"content-version":"vor","delay-in-days":21,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mycoses"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Bacterial aggregation has been shown to occur in synovial fluid which are resistant to high concentrations of antibiotics. Yet the propensity of <jats:italic>Candida<\/jats:italic> spp. to form aggregates is unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To assess the ability of numerous <jats:italic>Candida<\/jats:italic> spp. to form synovial fluid aggregates and the clinical ramifications of the aggregates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Nine different Candidal prosthetic joint infection clinical isolates were evaluated for their ability to form aggregates at static and dynamic conditions and their resistance to high concentrations of amphotericin. Furthermore, the ability of tissue plasminogen activator (TPA) to disrupt the aggregates and enhance amphotericin activity was assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The results show that all species of <jats:italic>Candida<\/jats:italic> spp. evaluated formed aggregates in synovial fluid under dynamic conditions that were resistant to amphotericin. Yet no aggregates formed in tryptic soy broth under any conditions or in synovial fluid under static conditions. As well, when TPA was combined with amphotericin there was a statistically significant decrease (<jats:italic>p<\/jats:italic>\u2009&lt;\u2009.005) in the amount of colony forming units per mL for all Candidal species evaluated. Interestingly, for <jats:italic>Candida krusei<\/jats:italic> there was no colony forming units observed after exposure to TPA and amphotericin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings suggest that Candidal species form synovial fluid aggregates that are resistant to high dose amphotericin similar to those that occur with bacteria. However, the varying ability of the different <jats:italic>Candida<\/jats:italic> spp. to form hyphae and pseudohyphae compared to yeast cells may have direct impacts on the hardiness of the aggregates and thereby have clinical ramifications with respect to treatment durations.<\/jats:p><\/jats:sec>","DOI":"10.1111\/myc.13769","type":"journal-article","created":{"date-parts":[[2024,7,23]],"date-time":"2024-07-23T05:19:42Z","timestamp":1721711982000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Propensity of <i>Candida<\/i> spp. prosthetic joint infection clinical isolates to form aggregates in synovial fluid and the clinical ramifications"],"prefix":"10.1111","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4977-0968","authenticated-orcid":false,"given":"James B.","family":"Doub","sequence":"first","affiliation":[{"name":"The Doub Laboratory of Translational Bacterial Research University of Maryland School of Medicine  Baltimore Maryland USA"},{"name":"Division of Clinical Care and Research Institute of Human Virology, University of Maryland School of Medicine  Baltimore Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hamda","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"The Doub Laboratory of Translational Bacterial Research University of Maryland School of Medicine  Baltimore Maryland USA"},{"name":"Division of Clinical Care and Research Institute of Human Virology, University of Maryland School of Medicine  Baltimore Maryland 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